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A NEW LOOK AT THE ROLE(S) OF GLYCOGEN AND SUGAR PHOSPHATES IN SKELETAL MUSCLE CONTRACTILITY
Funder
National Health and Medical Research Council
Funding Amount
$193,224.00
Summary
According to textbooks, glycogen in skeletal muscle is a homogenous molecular species whose sole role in muscle contraction is that of a carbohydrate-energy store. Likewise, sugar phosphates, such as glucose1-phosphate (G1-P), glucose 6-phosphate (G6-P), fructose 6-phosphate (F6-P) and fructose 1,6-bisphosphate (F1,6-bP) are generally presented as negatively charged compounds that act only as substrates-products of intermediary reactions in sugar degradation pathways. However, there is now compe ....According to textbooks, glycogen in skeletal muscle is a homogenous molecular species whose sole role in muscle contraction is that of a carbohydrate-energy store. Likewise, sugar phosphates, such as glucose1-phosphate (G1-P), glucose 6-phosphate (G6-P), fructose 6-phosphate (F6-P) and fructose 1,6-bisphosphate (F1,6-bP) are generally presented as negatively charged compounds that act only as substrates-products of intermediary reactions in sugar degradation pathways. However, there is now compelling evidence that (i) glycogen depletion impairs muscle contractility even when there is no shortage of cellular energy, (ii) there are two molecular forms of glycogen, and (iii) sugar phosphates can act as potent modifiers of functional domains in muscle proteins. This project addresses a number of novel questions regarding the role (s) of glycogen and sugar phosphates in muscle contractility and the cellular mechanisms involved. The knowledge produced will further our understanding of the correlation between Excitation-Contraction coupling and different intracellular glycogen pools, and of the molecular basis of prolonged effects of sugar phosphates on the contractile machinery. Furthermore, this work should also generate valuable insights into complex physiological (e.g. fatigue and aging) and pathological (e.g. atherosclerosis, metabolic myopathies) conditions which are still poorly understood.Read moreRead less